Memory is a system in which nerves make complicated neural circuits in the brain with growth thereof, and specific information is consolidated in the neural circuits in a reproducible state. It was discovered that destroyed connecting synapses of nerves were restored in the hippocampus of the limbic system which is responsible for memory. It came to be inferred that new neural circuits are formed in the brain depending on the necessity for memory. It has also become revealed that hierarchical levels of memory exist, such as preservation of short-term memory and long-term memory and reproduction thereof. Short-term memory corresponds to a level that information is preserved only a short time, and then when it becomes necessary to memorize that information, the short-term memory changes to long-term memory, and this information is consolidated as memory which is not easily forgotten. It is considered that long-term memory is transmitted from the hippocampus to the cerebral cortex and stored in the cerebral cortex over many hours. Long-term memory is classified into declarative memory and procedural memory depending on a content to be memorized. Declarative memory is memory which can be explained by means of language, and procedural memory is what is called as memory of skill, which is acquired by a person and unconsciously used by the person. Declarative memory may sometimes be further classified into episodic memory and semantic memory. Episodic memory is memory of personal experience and semantic memory is that of general knowledge and information such as those acquired by study. The episodic memory is mainly obstructed in the Alzheimer disease, and in the disease, patients often cannot memorize experiences, i.e., what, when and where they have done.
Retinoid is a generic term for referring to compounds that bind to receptors required for all trans-retinoic acid and 9-cis-retinoic acid to exhibit physiological functions thereof (three kinds of subtypes of the receptor exist for each compound), and thereby exhibit actions similar to those of retinoic acid or a part of the actions. Concerning the action of retinoid on neurodegenerative diseases, for example, it has been suggested that the retinoids described in Japanese Patent Unexamined Publication (KOHYO) No. 2000-502707 are effective for neurodegenerative diseases (e.g., Alzheimer disease). It has also been reported that expression of dopamine D2 receptor is increased by activation of a retinoid receptor (Proc. Natl. Acad. Sci., USA, 94, pp. 14349-14354, 1997). As for relationship between a retinoid and memory, it has been reported that reduction of memory in aged mice is recovered by retinoic acid (150 μg/kg, s.c.) (J. Neurosci., 21, pp. 6423-6429, 2001). However, what is suggested in this article is suppression of reduction of already consolidated long-term memory by retinoic acid, and the article does not suggest nor teach any action of retinoic acid on the consolidation process of short-term memory to long-term memory.
[Patent document 1] Japanese Patent Unexamined Publication (KOHYO) No. 2000-502707
[Non-patent document 1] J. Neurosci., 21, pp. 6423-6429, 2001